Immunology Flashcards
The Immune system
The immune system is an organised system of organs, cells and molecules which interact together to defend the body against disease.
Microbes
- Viruses
- Bacteria
- Fungi
- Protozoa
(in order of increasing size nm - mm)
We encounter many of these on a daily basis, many are good, most do no harm leaving only a very small number of pathogens (disease causing microbe).
Organs of the immune system
Primary lymphoid organs - Production of white blood cells.
Bone marrow - Source of stem cells which develop into the innate and adaptive immune responses.
Thymus - ‘School’ for T cells. Where developing T cells learn not to react to self (autoimmunity).
Secondary lymphoid organs - Sites where the immune responses are initiated.
Lymph nodes - Located along the lymphatic vessels. Lymph fluid from blood and tissue is filtered. Site of initiation of immune responses.
Spleen - Site of initiation for immune responses against blood-borne pathogens.
Tonsils
3 Layers of defense
- Chemical and physical barriers - stop pathogenic or disease causing organisms from getting into our body.
- Innate ‘arm’ - React very quickly to try and destroy invading microbe.
- Adaptive ‘arm’ - Largely orchestrated by T cells and B cells. Can make antibodies and form memory cells.
Physical barrier - Skin
Epidermis - Outer layer. Dead cells, keratin and phagocytic immune cells. Largely made up of layers of dead cells.
Dermis - Inner layer. Thick layer of connective tissue, collagen and blood vessels and phagocytic immune cells.
Skin is constantly shedding meaning there is constant renewal. This helps to get rid of and fight microbes which get o our skin.
Phagocytic immune cells
Engulf microbes to destroy them.
Dendritic cells are an important phagocytic cell which links the innate and adaptive ‘arms’ together.
Many myeloid cells are phagocytic - neutrophils, macrophages, dendritic cells.
Chemical defences of the skin
- Antimicrobial peptides - eg skin defensins
Form pores in microbial cell membranes causing it to leach out its nutrients and die. - Lysozyme - breaks down bacterial cell walls
- Sebum - Low pH, antimicrobial as microbes don’t like acidic environments produced by sebaceous glands at the base of hair on our skin.
- Salt - hypertonic environment can desiccate (dry out) microbes. Produced in sweat in the sweat glands.
Mucous Membranes
Line parts of our body that are inside our body but come in contact with air and lead to the outside. eg urinary tract, respiratory tract, eyes, nasal passage, gastrointestinal tract etc.
Epithelium layer is composed of tightly packed live cells, constantly renewing. Also contains mucus-producing goblet cells which produce a mucus layer across the top surface of the mucous membrane for protection.
Mucociliary escalator
Functions to get things which we’ve inhaled but shouldn’t have out of our lungs and back up (so we can swallow it or cough it out).
Cilia located on the surface of some cells which line the respiratory tract. Cilia will move the mucus which contains particles like dust, bacteria etc up.
Other chemical defenses on mucosal surfaces
Tears - Flush away microbes in our eyes
Stomach - Low pH - too acidic for microbes
Gall bladder - Bile which is antimicrobial
Intestine - Digestive enzymes which break down most bacteria.
Mucus
Defensins
Lysozyme (in tears and urine)
Skin vs Mucous membrane
- Number of cells layers - Skin = many, Mucous = 1 - a few
- Tightly packed cells? - Both = Yes
- Cells dead or alive? - Skin = outer layer is dead, inner layer is alive, Mucous = Alive
- Mucus present? - Skin = No, Mucous = Yes
- Lysozyme and defensins? - Skin = Yes, Mucous = some cases
- Sebum? - Skin = Yes, Mucous = No
- Cilia present ? - Skin = no, Mucous = In trachea and uterine tracts
Note - Constant flow of fluids through the gut is another mechanism which is antimicrobial.
Innate
Rapid response (almost immediate = mins to hours)
Already in place (waiting and ready to act when microbe invades)
Fixed (same response for every microbe)
Limited specificities (not able to recognise many differences between different microbes)
Has no specific memory
Innate responses include:
Surface barriers = skin, mucous membranes
Internal Defences = phagocytes, natural killer cells, inflammation, antimicrobial proteins, fever.
Adaptive
Slow (days to weeks)
Improves during the response
Variable
Highly specific (can tell 1 strain of a virus from another strain)
Has long term specific memory
Essential for fighting against intracellular pathogens such as viruses.
Adaptive response includes:
Humoral (antibody) immunity = B cells
Cellular immunity = T cells
Blood
Composed of plasma and cells.
Plasma (55%) = proteins, other solutes and water
Formed elements (45%) = Platelets, white and red blood cells
Bone marrow
Bone marrow stem cells = source of blood cells (stem cells differentiate into all different kinds of cells).
This process is called hematopiesis.
3 blood cell lineages:
- Erythroid = red blood cells
- Myeloid = granulocytes, monocytes, dendritic cells, platelets (innate immune cells)
- Lymphoid = B and T lymphocytes (adaptive immune cells)
Note - white blood cells (leukocytes) = myeloid + lymphoid.
Granulocytes
In blood:
Granulocytes circulate in the blood and can move into tissue during inflammation.
Neutrophils - 75 % of all leukocytes. Highly phagocytic “eat and kill”, numbers in blood will increase during infection.
In tissue:
Mast cells - Line mucosal surfaces. Release granules - (performed chemicals stored in the cytoplasm) ie degranulate to send chemical signal to other cells and attract white blood cells to areas of tissue damage (inflammation / infection).
Phagocytic cells
Monocytes = present in blood (prominent nucleus). Low phagocytosis, when they leave the blood they develop into macrophages in the tissues, such as spleen and liver.
Macrophages = quite large. High phagocytosis. Can either be migratory (move from blood to tissue and then leave again) or they will stay in the tissue and become resident (sessile).
3 functions:
1. Phagocytosis
2. Communicate with other cells through the release of chemical messengers (messenger released by an immune cell and bind to another immune cell on the surface to warn the cell theres danger or tell that cell to change so its ready for the infective agent).
3. Show information about pathogenic microbes to T cells.
Dendritic cells
Linking innate and adaptive immune responses.
Found in low numbers in blood and in all cell tissues in contact with the environment, as their potent (don’t need many to do what they do).
Phagocytic
Most important cell in triggering the adaptive immune responses.
Movement of cells in the immune system
Cells are carried in the blood and lymph, they can leave the blood to enter tissues. Lymph in tissues collects into lymphatic vessels which drain lymph into lymph nodes.
For example, if we had an infection in our big toe, dendritic cells in the big toes would move into lymphatic vessels and drain into a local lymph node where they an interact with other immune cells like T cells
How do our innate cells recognise pathogens
Different types of microbes have the same building blocks. There are common molecular patterns that recur with certain pathogens. These are known as PAMPS - pathogen-associated molecular patterns, these are not very specific.
Common building blocks of viruses
- Nucleic acid = single or double stranded RNA.
When viruses go into cells they will remove their nucleocapsid and envelope leaving naked nucleic acid.
Thus our immune system can recognise nucleic acid.
Common building blocks of bacteria
- Cell Wall = lipopolysaccharide (LPS), endotoxins, lipoteichoic acid
- Flagella = flagellin (protein)
- Nucleic acid = unmethylated CpG DNA. Bacteria DNA has lots of C and G bases together and are unmethylated compared to our DNA which is methylated.
Thus our immune system can recognise unmethylated CpG in the DNA
Pattern Recognition Receptors (PMR)
PMR are expressed on the surface or on the inside of the cell and are able to recognise PAMPS.
If a PAMP binds with a receptor, a signal will be sent down to the nucleus telling it to up-regulate gene transcription and start making proteins needed to fight the infection.
Receptors on the surface of the cell can recognise bacterial cell wall components whilst receptors internally in phagolysosomes which bacterial and viral nucleic acids can bind to, sending the same signal to the nucleus.
Fever / Pyrexia
Will encounter a fever if you have an infection.
Signs of fevers = abnormally high temperature > 37 degrees.
Arises when signals to the hypothalamus to set the thermostat, tell it to reset and that the body needs to be hotter, this causes the body to feel cold.
This is caused by pyrogens - cells released by the immune system.
Pyrogens include chemical messengers such as the cytokine interleukin 1 (IL-1) which are produced by cells that are highly phagocytic.
When the phagocytes stop engulfing things, IL-1 decreases, causing the temperature to decrease back down to its normal level.
Why does our body need to be hotter?
Hotter temperatures can inhibit some microbes from growing.
Can also cause our immune system to improve its function
Thus a slight temperature can be beneficial in fighting infections but a temperature too high can be dangerous.
The inflammatory response
A nail goes into our foot:
- Mast cells will release chemical signals sending out messages from resident cells to attract more cells to the site of injury / infection.
- Neutrophils generated in the bone marrow will enter the blood (leukocytosis). If they receive signals from these chemoattractant chemicals being released by mast cells they will begin to move from the blood to the tissue. This happens because :
- Neutrophils will slow down and cling to the capillary wall (Margination).
- The signals also tell the blood vessels to dilate, making them bigger resulting in more cells in that are and slower movement of the cells.
- Signals also tell the blood vessels to become ‘leakier’ which enables the neutrophils to squeeze out through the vessels walls (diapedesis).
- They will then follow the chemical trail to the site of injury (chemotaxis)
Phagocytosis Stage 1
inflammatory response continued
Phagocyte adheres to pathogen or debris:
Happens through receptors on the phagocytes membrane which are able to recognise bacteria thats been opsonized (like a sticky note on its head saying ‘eat me’).
Things which can opsonise bacteria:
- complement
- antibody
Phagocyte receptors can bind to these and if they have labelled bacteria, then they’re effectively binding to the bacteria.
Phagocytosis Stage 2
Phagocytic cell is triggered to form a pseudopod, that eventually engulfs the particles forming a vesicle called a phagosome.
Phagocytosis Stage 3
The phagocytic vesicle can fuse together with a lysosome forming a phagolysosome.
Phagocytosis Stage 4
Lysosomes are filled with toxic compounds and enzymes as well as a very acidic environment that will degrade and destroy the pathogens.
Phagocytosis Stage 5
Through exocytosis the vesicle will get rid of any indigestible and residual material.
Lysosome
Low pH: Acidic environment Toxins: Reactive oxygen intermediates (hydrogen peroxide) and reactive nitrogen intermediates (nitric oxide). Enzymes: Proteases - digest proteins Lipases - digest lipids Nucleases - digest nucleic acid
Tuberculosis
Contains molecules which stops the lysosome fusing with the phagosome, and thus is able to live in the phagosome.
Complement System Cascade
Series of enzymatic reactions that occur in the blood and functions to have antimicrobial effects.
Complement system is made up of 9 major proteins / protein complexes (C1 - C9).
Acts like a waterfall, something happens to trigger it at the top, power generated at the bottom is much greater than the top ie the response is amplified.
There are 3 distinct pathways the complement system may be initiated. and 3 different outcomes from it.
3 Complement Pathways = Different triggers involving different complement proteins to start the cascade.
- Classical - Antibody bound to pathogen binds complement which triggers the cascade. (more of an adaptive response)
- Alternative - Pathogen binds complement to surface / pathogen component. (more of an innate response)
- Lectin - Carbohydrate components of microbes bind complement triggering the cascade.
All pathways converge to get C3 convertase (enzyme complex). C3 precursor molecules break into 2 smaller molecules - (active form) C3a and C3b.
As enzymes are activated they cleave they next thing in the series resulting in 3 different possible outcomes.
3 Outcomes of Complement Casacade
- Opsonisation -Label:
C3b binds to bacteria, making it more ‘tasty’. - Lysis -Destroy:
C9 causes membrane attack complex formation - Pores in bacterial cell leads to death. - Chemotaxis -Recruit:
Complement proteins act as peptide mediators of inflammation and recruit phagocytes.
Opsonisation - Label
Opsonisation = coating the microbe with:
- Complement fragment C3b.
Microbe is now labelled for phagocytosis (is more tasty) so can bind to a receptor on a macrophage that recognises C3b, triggering phagocytosis.
= Fast process
Lysis - Destroy
Assembly of MAC (membrane attack complex) by mostly C9. This will form a pore into the membrane of the bacterium causing lysis. Bacteria leaches out its contents so will die.
Chemotaxis - Recruit
Complement proteins C3a and C5a act as peptide mediator of inflammation and recruit phagocytes.
Antigen Sampling and Presentation
When bacteria are introduced into our tissue, dendritic cells which are present in major organs will phagocytose the microbe to form a phagosome. = Antigen recognition phase.
Pathogens are made up of proteins. Dendritic cells will break down this these proteins into peptides (chains of amino acids) which are unique to that pathogen. Some of these peptides will be loaded onto MHC (others may leave the cell through exocytosis).
Dendritic cells then migrate from organs into the lymphatic vessel and drain into a local lymph node where they can interact with cells from the adaptive immune system.
They will present peptides on the MHC proteins to other white blood cells - T cells and B cells.
T and B cell activation can take a long time to kick in. = Lymphocyte activation.
Adaptive Immunity
Antigen presenting cells (APC) such as dendritic cells present the peptides on MHC to 2 types of T cells - CD4 and CD8.
CD4 ‘helper’ T cells work by producing chemicals called cytokines which are sent to B cells and CD8 T cells. When the B cell recognises the same antigen it needs to receive the help signals from CD4 cells so it can be activated and differentiate into plasma cells which produce the antibodies. When cytokines need to be sent to the CD8 cells so they can also be activated to become cytotoxic T cells (CTL cytotoxic T lymphocytes) which can produce molecules to kill virus infected cells and cancer cells.
= Effector phase
As pathogens are killed, their numbers drop.
= Decline phase
Antigen
Antigens are anything that has the potential to be recognised by the immune system, (usually peptides for T cells).
- Foreign antigen = Transplants, pathogens, some chemicals ie anything from the ‘outside’.
- Auto (self)-antigen = Immune system normally tolerant to self-antigen. However self-antigen may be recognised in auto-immune disorders.
Purpose of antigen uptake:
- Clearance of pathogens (innate)
- For presentation to T cells (adaptive)
Adaptive immunity evolved in vertebrates
500 million years ago, phagocytes evolved to keep remnants of pathogens and display these to other cells of the immune system. (ie recycling the rubbish generated by the phagocytosis process). The adaptive immune system evolved from there.
All vertebrates have an adaptive and an innate immune system. However invertebrates have innate immunity only. (Jawless fish have their own adaptive immune system which differs to ours).
MHC Expression
MHC-I:
Expresses endogenous (intracellular) antigens.
Expressed on all nucleated cells. (thus no red blood cells)
Antigenic proteins are degraded into peptides within the nucleus and are then imported into the ER where peptide loading takes place. The antigen loaded on MHC-I then moves out to the surface of the cell.
MHC-II:
Expresses exogenous (extracellular) antigens.
Expressed only on antigen presenting cells.
Antigenic proteins are broken down in the phagolysosome. Peptide loading onto MHC-II takes place in the phagolysosome. Some of these will then be taken up to and expressed on the cell surface
T Cell
T cells are lymphocytes (white blood cells) that are specific for a particular antigen.
They get activated by APCs and then proliferate to make cytokines and cytotoxic molecules.
They destroy pathogens as well as help other immune cells destroy pathogens.
2 types = CD4 and CD8
Each T cell has a unique T cell receptor (TCR) specific for 1 peptide antigen.
Each T cells also has a co-receptor (CD4 or CD8 proteins).
T cells recognise MHC / peptide complexes.
T Cell Development
Bone marrow - Production of T cell precursors. These travel through the blood to the thymus.
Thymus - TCR gene arrangement
- Make T cells able to recognise antigens
- Get rid of T cells which recognise self antigens
Developed T cells then travel the the lymph nodes, spleen and blood.
T Cell development in the thymus
In the thymus T cells will build a T cell receptor.
This occurs when immature T cells (thymocytes) rearrange the variable parts of their TCR genes in the thymus.
The rearrangement process is essentially random, which creates diversity in T cell repertoire, meaning T cells can recognise all types of pathogens.
CD4 and CD8 T cells
CD4 recognise peptide antigen in context of MHC-II.
CD8 recognise peptide antigen in context of MHC-I.
The co-factors CD4 and CD8 proteins will bind to the MHC stabilising the interaction between the APC and the T cell.
T cell activation
T cells which have not been activated by a MHC / peptide complex are naive.
Activated T cells are known as effector cells.
Activated CD4 ‘helper’ T cells:
Produce cytokines which are sent to CD8 T cells (which are activated by MHC-I) to give them a boost so they can become fully activated. The cytokines also help B cells become activated.
Activated CD8 T cells :
Once fully activated with help from the cytokines, CD8 T cells can develop into cytotoxic T lymphocytes (CTL).
These will leave the APC and travel to the site of infection where they will find cells which also present MHC-I with the same peptide that activated that T cell. They will then recognise that this is the infected cell they are required to kill. They can then release perforin which will make a hole in the membrane of the cell, and granzyme which will enter the cell and kill it.
Memory T cells
T cell activation also results in the formation of memory T cells. Memory T cells (CD4 and CD8) reside in the body for long periods of time, and are specific for the same pathogen which activated the T cell.
Memory T cells become effector cells which are in a slightly different state to naive T cells, allowing them to perform their effector cell function much much faster in the case of repeat exposure to the same antigen. (days rather than weeks).
HIV - Human immunodeficiency virus
Receptor for HIV is CD4 molecule on CD4 T cells.
Infection leads to the loss of CD4 T cells.
Thus because these cells are needed to help activate B cells and CTL cells, the whole immune system starts to underperform, as the cells needed to fight infections cannot be activated. Consequently, the HIV infection impacts immunity to microbes (fungi, bacteria and virus) and to cancer.
B Cells
B cells are :
Lymphocytes which develop in the bone marrow
They express unique antigen receptors (BCR)
Plasma cells are activated B cells that secrete antibody
Memory B cells provide memory
B cell development
Developed in the primary lymphoid organs:
B cells develop in the bone marrow and then go into the periphery.
Perform function in the secondary lymphoid organs:
B cells will be waiting in the lymph nodes and spleen where they will be activated.
B cells Structure
B cells have a large nucleus.
Surface of each B cells is covered with around 100,000 BCR. (Mainly IgM / IgD antibodies)
BCR structure:
Composed of 2 heavy chains (larger / inner) and 2 light chains (smaller / outer). (Forms a Y structure)
The region at the top of the Y between the chains is called the variable region which can bind to the antigens.
BCRs are unique so only bind with specific antigens. They are able to recognise native antigens (ie antigens don’t need to be processed or presented on MHC like T cells require).
When this occurs they will become plasma B cells and secrete antibodies.
Antibodies
They’re the same as the BCR.
ie the same structure and specificity, just without being embedded in a cell membrane.
Functions of Antibodies - NOC
Neutralisation: (Viral)
Antibody specific for this virus will cover the whole virus completely so that it doesn’t have access to receptors which it needs in order to get into cells. Thus the antibody neutralises the activity of the virus.
Opsonisation:
Antibody specific to a particular antigen on the bacteria surface will coat the bacteria making them more tasty, and thus more likely to be opsonised and destroyed by a phagocyte.
Complement:
Antibody binds to antigen on pathogen membrane to help activate the complement proteins which help to kick off the formation of MAC, creating pores. This will destroy the cell.
Types of Antobodies
Antibodies need to be able to clear:
- different pathogens
- at different sites of the body
- replicating pathogens
Therefore we have different types of antibodies = antibody isotopes.
The B cell production of antibody response will change throughout the course of the immune system.
IgM
IgM is a pentamer (+ J chain).
The BCR on naive B cells are IgM antibodies, thus IgM is the first antibody isotope in the adaptive response after initial exposure to an antigen.
Function:
- Very effective at activating complement (best first defence mechanism).
- Targets extracellular bacteria
IgG
IgG is a monomer.
It is the main isotope for pathogens as it is the most abundant isotope in the blood.
Function:
(As the immune response goes on we need something a bit more stable and long lasting than IgM).
- Opsonisation
- Neutralisation
Thus targets bacteria and viruses
- Only Ig class which crosses the placenta to provide passive immunity.
IgA
IgA is a dimer (+ J chain and secretory component)
Is it the isotope at mucosal sites.
It is monomeric form in blood but when it gets to mucosal sites it forms a dimer = more stable in these environments.
It is present in secretions such as tears, saliva, mucus and breast milk.
Functions:
- Defence of mucous membranes including the gut.
- Targets bacteria and virus
- Present in breast milk so confers passive immunity on nursing infant.
IgE
IgE is a monomer.
It is the isotope which helps to destroy parasites (complex pathogens).
Present in low concentrations in the blood.
Functions:
- Immunity to multicellular parasites
- When antibody binds to antigen on the parasite, the other end of the antibody cross links with mast cells. This triggers mast cell to empty its cytotoxic molecules destroying the parasite.
- Causes allergic reactions
IgD
IgD is a monomer
Expressed on naive B cells
Function:
- Specific function unknown
- Can act as a antigen receptor (BCR)
Passive Immunity for babies
Mothers IgG crosses placenta during pregnancy
= main antibody required by babies.
IgA in breastmilk transferred to infant.
These antibodies enable the baby to have an immune response until it is able to fully develop its own.
Memory B Cells
When B cells are activated by an antigen and cytokines from CD4 T cells, in additions to plasma cells being formed, a small number of stimulated B cells form a pool of memory B cells.
Memory B cells persist for years in the blood and lymph. They express antibody only as BCR, and do not secrete any antibody. On repeat exposure to the same antigen which activated the B cell, they respond rapidly to become plasma cells and secret antibody.
Primary and Secondary B cell Immune Response
Primary :
Naive B cells need to be activated, Takes around 7 - 14 days before sufficient antibody is produced to eliminate the pathogen. (This is because they have to be activated, receive signals from CD4 cells, grow into plasma cells and then finally release antibodies)
Relatively low amounts of antibody produced - mainly IgM. Slow response but still works.
Secondary:
Relies on memory B cells
Fast response - 2-3 days before sufficient antibody is produced to eliminate the pathogen - mainly IgG.
Much higher amounts and better antibodies are produced.
Basis of Vaccination
Vaccines develop a primary response in our body in order to prepare our memory cells if the pathogen comes so they can quickly and effectively kill the pathogen.
If we do get repeat exposure to the antigen, our memory cells will cause huge production of better antibodies (mainly IgG). Lots of antibodies means the chances of finding and invigorating the immune response is much greater and faster.
2 Components of a Vaccine:
1. Antigen (usually a virus)
Usually attenuated - best way to attenuate a virus is to passage it through numerous cells so it becomes less and less effective.
2. Adjuvant:
Helps enhance the immune system by stimulating the cells in the region to get in there and cause more white blood cell lymph filtration.
Interconnected Innate and Adaptive Response
The innate and adaptive immune responses are not seperate, but actually an interconnected complex response.
The innate response is the first call of defense and critical at taking out the main force of microbes. (particularly important in response against bacterial pathogens).
It targets the early stages of microbial pathogenesis (adherence, invasion and replication)
The Adaptive response is essential in fighting against intracellular microbes such as viruses.
It targets the later stages of microbial pathogenesis
Antimicrobial Peptides - Defensins
Produced in our skin, gut and airways.
There are different types depending on location.
Active against gram positive and gram negative bacteria.
Defensins will land on strongly charged bacterial membranes and bind to them as they’re different to plant’s and mammals membranes which only have weak charges. They can then disrupt the bilayer. They may also disrupt membrane-bound machineries.
Lysozyme
Produced in skin and airways.
Especially active towards gram positive bacteria.
Lysozyme break the bonds between the glycopeptides (sugar in cell wall) ie breaks NAM and NAG apart.
This causes the cell wall to fall apart so the bacteria will dies.
Lysozyme is produced in tears but highest levels are present in human breast milk.
Detection of relative age of virus
As IgM is the first antibody produced in the adaptive immune repsonse, if we find IgM in a blood sample this indication the virus is recent.
However if we find IgG , this indicates the virus may be a bit older.
SCID -Severe combined immunodeficiency
A rare genetic disorder characterised by the disturbed development of functional T and B cells.
Without functional T and B cells, the person can not have any type of adaptive immune response.
Rheumatoid Arthritis (RA)
A good example of an autoimmune disorder. ie what happens when our immune system attacks self.
RA primarily affects joints such as synovial joints.
Allergic Reactions
Also caused by our immune system not working properly.
Peanut allergy is one of the worst and most widespread allergies. Caused by the problem of our body not knowing the difference between allergens and microbes.
Composed of 2 phases:
Sensitisation phase and Allergic reaction phase.
Sensitisation phase
Allergens (type of antigen) are picked up by dendritic cells and loaded onto MHC class molecules before interacting with a range of lymphocytes. The dendritic cells stimulate the production of CD4 helper T cells which stimulate the production of plasma cells. These plasma cells produce the antibody IgE. IgE will find their way to mast cells which are located all throughout the body. Mast cells have special receptors on their surface which can catch the FC region (non specific side) of the IgE antibody. Thus IgE antibodies specific for that antigen / halogen will cover the mast cell.
Allergic Reaction phase
Allergens (after repeat exposure) will come in contact with these mast cells covered in IgE. Ag induces cross linking of IgE bound to mast cells which stimulates the mast cells to degranulate and release granules such as histamines. There are what cause the symptoms from an allergic reaction.
This allergic response is almost immediate.
(Normally there will be no allergic reaction because the body is able to recognise that self-produced antigens are a non-threat to avoid the autoimmune response.
